tbuckley/cabot-search huggingface dataset:
Prognostic significance of immune-related adverse events and immunosuppression in patients with melanoma receiving adjuvant anti-PD-1 therapy.
Authors: Andrew David Knight, Lilit Karapetyan, Sabrina Bruno, Hassan Mohammed Abushukair, Na Bo, Hong Wang, Cindy Sander, John M. M. Kirkwood
Journal: Journal of Clinical Oncology (2023)

9580 Background: Treatment with anti-Programmed Death-1 (PD-1) therapy reduces the risk of recurrence for patients (PT) with resectable Stage IIB-IV melanoma (MEL). This treatment is associated with the development of immune-related adverse events (irAEs), which may necessitate use of immunosuppressive therapy and treatment discontinuation. This project investigates the impact of irAE and immunosuppressive therapy in survival outcomes of PTs with MEL. Methods: PTs with stage IIB-IV resectable MEL who received adjuvant or neoadjuvant treatment with anti-PD-1 therapy were enrolled from the University of Pittsburgh Melanoma Center biospecimen repository. The association between irAEs/immunosuppressive therapy and recurrence-free survival (RFS) and overall survival (OS) were evaluated by univariate and multivariate Cox proportional hazards regression models. Results: A total of 6059 PT were consented to the repository: stage III = 1,328, stage IIB = 403, and stage IIC = 269 PT. Of these PT, 180 men and 93 women received adjuvant anti-PD-1 therapy. Average age at diagnosis was 61. BRAF mutation present in 94 PTs: V600E = 71 PT, V600K = 11 PT. Documented irAEs occurred in 50.9% of PTs. Cutaneous irAEs were most common (65/139, 46.8%), followed by endocrine (45/139 32.4%), and visceral organ (37/139, 26.6%). Of the 32 visceral organ irAEs, 15 were gastrointestinal, 10 pulmonary, 5 hepatic, and 1 renal. Systemic corticosteroids &gt; 10mg of prednisone equivalent were administered during adjuvant therapy for 24.9% of PT. In the univariate model, development of irAEs was associated with improved OS (HR = 0.38; CI 0.18-0.83, p = 0.015). In a multivariate analysis after adjusting for age and sex, irAE development continued to be associated with improved OS (HR = 0.38; CI 0.17-0.82, p = 0.014). RFS did not differ for patients that developed irAEs (HR = 0.9; CI 0.59-1.4, p = 0.67). Steroid treatment was not associated with a change in OS (HR = 1.04; CI 0.46-2.4, p = 0.93) or RFS (HR = 0.96; CI 0.59-1.56, p = 0.87). Conclusions: Half of stage IIB-IV resectable MEL PT receiving adjuvant anti-PD1 therapy developed irAEs, of which 24% required steroid therapy. Development of irAE was associated with improved OS and corticosteroid use for irAE did not mitigate adjuvant therapy outcome benefits.
Diverse genomic characterization of Chinese patients with osteosarcoma and soft tissue sarcoma.
Authors: Mengxiong Sun, Fei Quan, Huan Yi, Zhongyu Lu, Yangyang Yu, Siqi Chen, Ran Ding, Wanglong Deng, Fanfeng Bu
Journal: Journal of Clinical Oncology (2023)

e23528 Background: Osteosarcoma(OST) differs from soft tissue sarcoma(STS) in terms of pathology and chemotherapy, but there is partial overlap in targeted therapy. Few articles have described the differences in genetic profiles of OST and STS in Chinese patients based on extensive sample data, at this point, identifying the difference genomic characterization between them may provide new drug targets for clinical diagnosis and treatment. Methods: A 551-gene targeted panel of DNA-based Next Generation Sequencing (NGS) assay was performed on tumor tissue(n = 613) and plasma(n = 136) obtained from STS(n = 586) and OST(n = 163) patients, the majority were male(n = 430, 57.4%), median age was 49(range 1-87), 101 patients also measured additional 67 gene fusions based on RNA-seq in tumor samples. All variants (SNV, INDEL, CNV and fusion) were entered into the result analysis. PD-L1expression was tested by IHC(SP263). Results: The top 5 mutant genes were TP53(28%), CDK4(20%), MDM2(18%), CDKN2A(15%), CDKN2B(15%) in STS, and TP53(26%), MYC(19%), CDK4(18%), MUC16(13%), CDKN2B(13%) in OST respectively. MDM2(18% vs 10%, p = 0.030) and PTEN(11% vs 4%, p = 0.007) were significantly higher in STS, while GNAS(7% vs 3%, p = 0.045) and IDH1(5% vs 1%, p = 0.002) were more common in OST. The most frequently affected pathways were Cell cycle(42%), Genome integrity(34%), RTK signaling(27%) in STS and Cell cycle(36%), Genome integrity(33%), transcription factor(28%) in OST. Additional significantly co-altered genes were RB1/PTEN, LRP1B/FAT3, FAT2/SPTA1 in STS, and MUC16/LRP1B, LRP1B/POLE, MED12/STAG2 in OST. More rare fusions were identified in STS. Wefound 15 PTPRB fusions, 14 of which were from STS. MDM2 fusions only detected in STS, 8 of which were from liposarcoma. Almost all patients were defined as MSS(625/629), with only 4 MSI-L and no MSI-H. 2.9%(17/589) STS and 3.1%(5/163) OST scored as TMB-H(≥10.00 Muts/Mb). TP53(p＜0.001), MUC16(p＜0.001), LRP1B(p＜0.001), FAT3(p＜0.001)were more likely to appear in the TMB-H group of STS, while MUC16(p＜0.001) was more likely to appear in TMB-H group of OST. 32.3%(83/257) STS and 29.6%(8/27) OST were PD-L1-positive(PD-L1≥1%). In STS, PDCD1LG2(p＜0.001), CD274(p＜0.001) and JAK2 (p = 0.001)were more common in the PD-L1-positive group, while MDM4 (p = 0.018) and PARP1(p = 0.003)were more common in the PD-L1-negtive group. There were no statistically significant differences due to limited PD-L1 data in OST. Conclusions: The analysis revealed that there are some differences in genetic profiles between Chinese OST and STS, which may provid more precise basis for personalized targeted therapy and immunotherapy.
Clinicopathological features and treatment profile of patients referred to a sarcoma medical oncology centre in India: Challenges and insights from the developing world.
Authors: Ghazal Tansir, Sameer Rastogi, Adarsh Barwad
Journal: Journal of Clinical Oncology (2023)

e23533 Background: Sarcomas are rare cancers that warrant expert pathologic diagnosis (dx) and multidisciplinary treatment (MDT). We analysed details of patients (pts) diagnosed with soft tissue sarcomas (STS) and bone sarcomas (BS) referred to our centre. Methods: This is a retrospective study of pts diagnosed with STS or BS referred to All India Institute of Medical Sciences, Delhi between January 2021 and December 2022. Histopathological discrepancies were noted as change of primary dx or differences in grading or sarcoma subtyping on pathology review. Surgical and/or medical deviations from standard practise were identified. SPSS 26.0 was used for statistical analysis. Results: 268 pts with median age of 35 years (range 8 months-85 years) and male predominance (n = 140, 52.2%) were included. 121 (45%) pts belonged to adolescent and young age (AYA) group. 163 (61%) pts came from urban/semi-urban background and from a median distance of 90 miles (range 6.2-1587). Median symptom duration prior to referral was 9 months (range 6 months-12 years). Based on biopsy or cytopathological evidence, referred pts included 186 (69.4%) with STS, 73 (27.2%) with BS, 7 with undifferentiated sarcoma (2.6%) and 2 with carcinoma (0.7%). The most common STS (n = 186) were leiomyosarcoma (14%), synovial sarcoma (12%) and liposarcoma (8.3%); BS (n = 73) included osteosarcoma (44%), Ewing sarcoma (44%), chondrosarcoma (9.5%). Molecular and/or germline mutation tests were performed only in 9 of 131 (6.8%) indicated cases before referral. Localized/locally advanced and metastatic stages were found in 94 (35.6%) and 116 (43.2%) resp; rest (21.2%) did not undergo staging work-up outside. Common primary sites were extremity (n = 127, 44.4%), abdomen (n = 71, 24.8%), thorax (n = 24, 8.3%). 125 (43.7%) and 91 (31.8%) pts had undergone surgery and chemotherapy resp outside. 1st line chemotherapy (n = 85) was anthracycline-based (n = 65, 76.4%), ifosfamide-based (n = 6, 7%), gemcitabine-docetaxel (n = 5, 5.8%). 2nd line (n = 29) was gemcitabine +/- docetaxel (n = 7, 24.1%), anthracycline (n = 6, 20.6%), ifosfamide-based (n = 6, 20.6%), pazopanib (n = 6, 20.6%). Pathologic discrepancies found in 87 (30.4%) pts included change of primary diagnosis in 44 (15%), sarcoma subtype variation in 35 (12.2%) and benign disorder misclassified as malignancy in 5 (1.7%) pts. Deviations in chemotherapy (n = 43, 47.2%) included inadequate dose/cycles in 18 (42%), no chemotherapy despite indication in 8 (18.6%), non-standard regimens in 10 (23%) pts. Distance/rural residence did not correlate with pathology/treatment deviations. Conclusions: In this era of precision medicine and targeted oncology, our findings reflect the need for well-equipped diagnostic and treatment facilities. The lack of expert centres catering to pts with sarcomas remains a challenge in developing countries.
The association of body mass index with overall survival, progression free survival and locoregional control in head and neck cancer treated with curative-intent definitive chemoradiation.
Authors: Udit Chatterjee, Sung Jun Ma, Michael Khan, Sharon Santhosh, Mahnoor Hashmi, Jasmin Gill, Brian Yu, Austin Iovoli, Mark Farrugia, Han Yu, Anurag K. Singh
Journal: Journal of Clinical Oncology (2023)

e18062 Background: The prevalence of obesity is anticipated to increase with nearly 1 in 2 adults having obesity by 2030. Previous meta-analysis and prospective studies showed that both obesity and overweight BMI were associated with worse all-cause mortality, cancer-related mortality, and the incidence of multiple types of cancer. Combined modality therapy, such as chemoradiation, often results in significant morbidity among patients with head and neck cancer (HNC). The association of BMI with treatment response, tumor recurrence, and survival outcomes among HNC patients remains unclear. Methods: Our study included a total of 445 patients with non-metastatic head and neck cancer who underwent curative-intent definitive chemoradiation at the Roswell Park Comprehensive Cancer Center from 01/2005 to 01/2021. We evaluated overall survival (OS), progression-free survival (PFS), locoregional failure (LRF), and distant failure (DF). BMI was stratified by normal weight (18.5-24.9 kg/m 2 ), overweight (25.0-29.9 kg/m 2 ), and obese (30 kg/m 2 or higher). Evaluation was performed using Kaplan-Meier method, log-rank tests, Cox proportional hazard multivariable (MVA) analyses. Results: A total of 445 patients (373 male [83.8%], median [interquartile range] age, 61 [55-66] years; n = 107 with normal, n = 179 with overweight, and n = 159 with obese) were included for analysis. Median follow up was 48.1 months (interquartile range 24.7-74.9). On Cox MVA, only overweight was associated with improved OS (adjusted hazards ratio [aHR] 0.59, 95% confidence interval [CI] 0.39-0.91, p = 0.02) and PFS (aHR 0.51, 95% CI 0.34-0.75, p &lt; 0.001). On logistic MVA, overweight (adjusted odds ratio [aOR] 0.86, 95% CI 0.80-0.93, p &lt; 0.001) and obese (aOR 0.89, 95% CI 0.81-0.96, p = 0.005) were associated with complete metabolic response on follow-up PET-CT after treatments. On Fine-Gray MVA overweight was associated with reduction in LRF (aHR 0.30, 95% CI 0.12-0.71, p = 0.007), but not DF (aHR 0.92, 95% CI 0.47-1.77, p = 0.79). Being obese was not associated with both LRF (aHR0.63, 95% CI 0.29-1.37, p = 0.24) and DF (aHR 0.70, 95% CI 0.35-1.38, p = 0.30). Conclusions: When compared to normal BMI, overweight BMI was an independent, favorable prognostic factor for complete response after treatments, OS, PFS and a reduction in LRF. Further investigations are warranted to improve our understanding on the role of BMI among patients with HNC.
A dual institution real-world study of avelumab for advanced Merkel cell carcinoma.
Authors: David Michael Miller, Kayla Wright, Ann W. Silk, Manisha Thakuria, Sophia Shalhout
Journal: Journal of Clinical Oncology (2023)

e21514 Background: Merkel cell carcinoma (MCC) is a rare, aggressive, cutaneous neoplasm with an increasing incidence rate and poor prognosis. The treatment landscape has changed dramatically over the last half decade, beginning with the 2017 approval of the anti-programmed death-ligand 1 (PD-L1) monoclonal antibody avelumab. Accelerated approval for avelumab was based on data from the JAVELIN Merkel 200 study, which demonstrated an objective response rate (ORR) of 33% in previously treated subjects (≥2L). In the first-line (1L) clinical-trial setting, avelumab was associated with an ORR of 40% and a durable response rate (DRR) of 30%. There are limited data regarding the efficacy of avelumab in the real-world setting. Methods: We performed a Mass General Brigham (MGB) Institutional Review Board-approved retrospective study of patients with advanced MCC. Clinical data regarding the disease course, including diagnosis and treatment, were collected from the Electronic Health Record and stored in a REDCap database. Response category was assigned based on the text of the radiology reports and clinician notes. Analysis was performed in R. Results: 1249 patients with MCC were identified; 260 received systemic therapy; 54 were treated with avelumab (our primary analysis cohort, PAC). Median age of the PAC was 74 years. 80% were male. 83% had an initial ECOG of 0 or 1. 20% were immunosuppressed at the time of MCC diagnosis. The real-world response rate (rwORR) for all patients treated with avelumab was 45.83%. rwORR in the 1L was 53.57% and 35% in the second line and beyond. The median duration of treatment response in the 1L was 518 days and 144 days for ≥2L. Median progression-free survival was 158 days and 95 days, and median overall survival was 553 days and 323 days for 1L and &gt; 2L, respectively. Conclusions: Our study provides important data about the real-world treatment of patients with advanced MCC. The response rate and progression-free survival were consistent with those observed in other real-world studies as well as the clinical trials. While the subjects studied in previously published studies differ from that in MGB cohort, the overall body of literature continues to demonstrate positive outcomes attributable to avelumab monotherapy in both the 1L as well as second-line or beyond and in patients with competent, as well as compromised, immune systems. Limitations of this study include its retrospective nature. Furthermore, given the small sample size, we are limited in making statistical inferences from the current data set and specific results may not be generalizable to all patients with MCC.
Comparing the time toxicity of cancer treatments in the CCTG LY.12 trial.
Authors: Arjun Gupta, Annette E. Hay, Michael Crump, Marina Djurfeldt, Liting Zhu, Matthew Cheung, Lois E. Shepherd, Bingshu E. Chen, Christopher M. Booth
Journal: Journal of Clinical Oncology (2023)

12135 Background: When different cancer treatments have similar oncologic outcomes, their respective time-related burdens can aid patient-oncologist decision-making regarding which treatment approach to pursue. We have previously developed a pragmatic and patient-centered metric of these time burdens-- which we term ‘’time toxicity’’-- as any day with physical healthcare system contact. This includes outpatient (e.g., bloodwork, scans, clinician, etc.) and emergency room visits, and overnight stays in a healthcare facility. Herein we sought to assess time toxicity in a completed RCT. Methods: We conducted a secondary analysis of the Canadian Cancer Trials Group LY.12 RCT that evaluated 2-3 outpatient cycles of gemcitabine, dexamethasone, and cisplatin (GDP) vs. dexamethasone, cytarabine, and cisplatin (DHAP) in 619 patients with relapsed/refractory lymphoma prior to stem cell transplant. Primary analyses reported similar response rates, transplantation rates, event-free-survival, and overall survival across arms. We calculated patient-level time toxicity by analyzing RCT forms. The study period was the date of assignment to the date of progression or the day before stem cell transplant. We considered days without healthcare contact as ‘’home days’’. We compared time measures across arms. Results: The median study duration was longer in the GDP arm (50, vs. 47 days in the DHAP arms, p=0.007). Median time toxic days were comparable in both arms (18 vs 19 days, p=0.79), but median home days were higher in the GDP arm (33 vs 28 days, p&lt;0.001). The proportion of time toxic days (time toxic days divided by study duration) was lower in the GDP arm (34%, vs. 38%, p=0.009). The GDP arm experienced more time toxicity related to planned outpatient chemotherapy (median, 10 vs. 8 days), but the DHAP arm experienced many more hospitalization days (median, 11 vs. 0 days) (Table). Conclusions: This study demonstrates that measures of time toxicity can be extracted from RCTs. These measures can add clinical insight into patient burdens. In LY.12, despite broadly comparable short- and long-term oncologic outcomes, the GDP arm experienced less time toxicity. Such information can guide decision-making for patients with aggressive hematological cancers, who already spend a significant portion of time with healthcare contact. Clinical trial information: NCT00078949 . [Table: see text]
Repetitive presentations of phase II and III trials involving systemic therapies in gastrointestinal (GI) malignancies at international meetings in the past few years.
Authors: Malu Barbosa, Artur Rodrigues Ferreira, Ricardo Lima Coelho, Pamela Carvalho Muniz, Camila Brambilla Souza, José Ap. Tristão Neto, Fanny Cascelli, Matheus Costa e Silva, Renata D'Alpino Peixoto
Journal: Journal of Clinical Oncology (2023)

e18638 Background: The American Society of Clinical Oncology (ASCO) and the European Society of Medical Oncology (ESMO) annual meetings as well as their GI dedicated meetings (ASCO GI and ESMO GI) have the premise to accept abstracts for oral presentations that have not been previously presented. Methods: We conducted a review of all 220 abstracts involving phase II or III trials of systemic therapies that have been presented orally from June 2019 to January 2023 at ASCO, ASCO GI, ESMO and ESMO GI meetings to evaluate the incidenceof repetitive presentations of the same trial in different meetings as well as their relationship to pharmaceutical industry sponsorship. ANOVA test was used to compare means between different groups and p values of ≤ 0.1 were considered significant. Results: Overall, 20,9% of accepted oral abstracts from phase II or III trials were replicated during the 4-year time frame. Of them, 39% were phase II, 61% phase III, 72% pharma sponsored, 39% included developing countries, and 59% were positive. The association of industry sponsorship and study positivity indicated a variation of up 3,55 appearances (p 0,017) in the number of times this research was orally presented. Conclusions: Our findings suggest that almost 20% of oral abstracts involving systemic therapies in GI cancers are presented more than once at relevant meetings, especially those with positive results and sponsored by pharma. Our study highlights the need for a more effective oral abstract selection system in oncology meetings.
Interpersonal concerns of young adult surgical oncology patients with advanced cancer diagnoses: A mixed methods study.
Authors: Beatrice J. Sun, Emily Pang, Byrne Lee
Journal: Journal of Clinical Oncology (2023)

e24225 Background: Incidence of cancer in young adults (YA) is increasing. YA patients with advanced cancer are more likely than elderly counterparts to undergo elective or palliative surgeries. A diagnosis of advanced malignancy poses unique social and emotional burdens on YA. This study aims to understand the experiences of YA cancer patients in managing interpersonal relationships and social expectations. Methods: This mixed-methods study consisted of cross-sectional patient quality of life (QOL) surveys (Functional Assessment of Cancer Therapy: General [FACT-G]), caregiver QOL surveys (Caregiver QOL – Cancer [CQOLC]), and semi-structured qualitative interviews with patients. Participants were YA ages 18-45 years with advanced-stage cancers, recruited from surgical oncology clinic at a tertiary academic institution. Interviews were transcribed and analyzed by two independent reviewers to describe themes (italicized) on social and interpersonal impacts of patients’ cancer diagnosis. Results: Interviews and patient surveys were conducted with 18 YA patients. Median time since cancer diagnosis was 15 months, 44% of patients had metastatic disease at diagnosis, and 89% of patients had previously undergone both chemotherapy and surgery for cancer treatment. 56% of patients identified their spouse or significant other as the person they were closest to, and 28% were closest to a parent or sibling. 56% of patients had children of their own who lived in the household. Median FACT-G scores were 23/28 for social/family well-being (IQR: 18-25) and 13/28 for emotional well-being (IQR: 8-17). Caregiver surveys were completed for 12 of 18 patients, revealing that most developed a closer relationship with their loved one (67%) and felt informed about their disease (92%). Qualitative interview analysis revealed themes of: information-sharing about cancer, where patients shared concerns of withholding prognostic information to give loved ones hope; impacted relationships with friends and colleagues, as patients struggled with who to disclose their cancer diagnosis to; social/physical perceptions by others, as patients worried about changes in their physical appearance (e.g. weight loss) as a result of cancer; financial concerns as a result of treatment and its future impact on the patient’s loved ones. Conclusions: This mixed methods study highlights the interpersonal concerns of YA with advanced cancers. At a phase where identity formation, social perceptions, and personal relationships may be threatened by cancer, unique psychosocial and emotional challenges arise. Programmatic changes are needed to provide appropriate support, resources, and empathetic care to this distinct population of cancer patients.